The present invention relates generally to the field of G-protein coupled receptors and, more specifically, to therapeutic and diagnostic compositions and methods relating to ADP-glucose receptor.
G-protein coupled receptors (GPCRs) comprise a large and growing family of integral membrane proteins which transduce extracellular signals into cellular responses. The natural agonists of different GPCRs range from peptide and non-peptide neurotransmitters, hormones and growth factors, to lipids, nucleoside-sugars, amino acids, light and odorants.
G-protein coupled receptors are involved in a variety of critical biological functions, and have proven to be important pharmacological targets. It is estimated that over 50% of current drugs are targeted towards GPCRs, and represent about a quarter of the 100 top-selling drugs worldwide. G-protein coupled receptors are also linked to a large number of hereditary diseases.
Thus, there exists a need to identify novel G-protein coupled receptors and their ligands, to identify the physiological function of such receptors, and to develop methods of screening for therapeutic compounds that specifically target these receptors. There also exists a need to identify individuals having or at risk of developing diseases associated with aberrant function or expression of G-protein coupled receptors. The present invention satisfies these needs and provides related advantages as well.
The present invention provides an isolated nucleic acid molecule containing a nucleotide sequence which encodes an ADP-glucose receptor. Further provided are vectors and cells containing the isolated nucleic acid molecule. The invention also provides an isolated polynucleotide, containing at least 20 contiguous nucleotides from the nucleotide sequence designated SEQ ID NO:1 or from the complement thereof.
Also provided is an isolated ADP-glucose receptor polypeptide. Further provided is an isolated immunogenic peptide, containing at least 10 contiguous residues of the amino acid sequence designated SEQ ID NO:2. The invention also provides an antibody specific for the isolated ADP-glucose receptor polypeptide, and an antibody specific for the isolated immunogenic peptide.
The invention also provides a method of identifying an ADP-glucose receptor agonist or antagonist. The method is practiced by contacting an ADP-glucose receptor with one or more candidate compounds under conditions suitable for detection of a G-protein coupled signal in response to ADP-glucose, and identifying a candidate compound that alters production of the signal. Such a compound is characterized as an ADP-glucose receptor agonist or antagonist.
Also provided is a method of identifying an ADP-glucose receptor ligand. The method is practiced by contacting an ADP-glucose receptor with one or more candidate compounds under conditions suitable for detecting selective binding of ADP-glucose to ADP-glucose receptor, and identifying a candidate compound that selectively binds the ADP-glucose receptor. Such a compounds is characterized as an ADP-glucose receptor ligand.
Further provided are methods of diagnosing or determining susceptibility to ADP-glucose receptor associated conditions. In one embodiment, the method is practiced by detecting in a sample from the individual expression of a nucleic acid molecule which specifically hybridizes to the complement of SEQ ID NO:1. Abnormal expression of the nucleic acid indicates that the individual has or is susceptible to an ADP-glucose receptor associated condition. In an alternative embodiment, the method is practiced by detecting in a sample from the individual expression of a polypeptide which specifically binds an ADP-glucose receptor ligand. Abnormal expression of the polypeptide indicates that the individual has or is susceptible to an ADP-glucose receptor associated condition.